The primary goal of the X-ray Crystallography Core Facility is to provide access to state-of-the-art hardware, software and expertise to Cancer Center laboratories that use X-ray crystallography as a tool to address questions in their research programs. The Core provides and maintains In-house equipment and computational resources for data collection, processing and structure determination, implements a wide range of crystallographic and structure analysis software packages, participates in multi-institutional consortia for long-term regular access to synchrotron beamlines, and provides training and technical assistance to users of both the in-house and remote facilities. In addition, the Core Head collaborates with non-structural MSKCC groups on macromolecular crystallization and structure-determination projects, and also provides modeling expertise and guidance to those laboratories that can benefit from the use of available structures in the design and interpretation of experiments. Understanding the biological processes involved in tumorigenesis has increasingly benefitted from structural investigations that provide key functional and mechanistic Insights, as well as atomic-level details important for drug discovery. Many of the questions require the structure determination of large proteins, assemblies and macromolecular machines. Advances in protein expression technologies and nano-liter crystallization robots are making it possible to obtain hitherto inaccessible crystals. However, crystals of such complexes often present major experimental challenges due to small crystal size, large unit cells, poor order and limited diffraction. The X-ray Core alms to help address these limitations for MSKCC investigators by providing the latest generation in-house X-ray diffraction systems, by testing and implementing new methods, tools and software and disseminating the latest improvements, and by participating in multi-institutional consortia that not only build and operate synchrotron beamlines, but also carry out technology research and development that push the envelope of beamline capabilities. The X-Ray Crystallography Core has supported 8 investigators in the past year. During the past grant period the Core has contributed to 115 publications of researchers from 3 programs.